Maternal folic acid and risk of autism in siblings

Evidence is conflicting on whether prenatal use of folic acid reduces risk of autism spectrum disorder (ASD) in offspring. A new study in JAMA Psychiatry has looked at that purported connection from a different angle, examining whether maternal folic acid intake is associated with rates of ASD in younger siblings of children with the condition.

The participants were mothers in Northern California who had a child with confirmed ASD and were planning a pregnancy or were pregnant with another child. Information on the vitamins and supplements they took (brand, frequency, dose and timing of maternal intake) was obtained through telephone interviews. The younger siblings’ development was assessed at age 3, and they were classified into 1 of 3 outcome groups: ASD, typical development (TD) or non-typical development (non-TD).

A total of 241 siblings were included—58.1% male and 41.9% female. Fifty-five children (22.8%) were diagnosed with ASD, 60 (24.9) children were diagnosed as non-TD, and 126 (52.3%) were confirmed with TD. Children with ASD were more likely to be male.

Prevalence of ASD among children whose mothers took folic acid in the first month of pregnancy was 14.1% (18) compared with 32.7% (37) in children whose mothers did not take folic acid during that time. After adjusting for maternal education, children whose mothers took folic acid in the first month of pregnancy were half as likely to receive an ASD diagnosis (adjusted RR, 0.50; 95% CI 0.30-0.81) or a non-TD outcome (adjusted RR, 1.14; 95% CI 0.75-1.75).

The authors found that the highest tertile (805-4800µg) of total mean folic acid supplemental intake during the first month of pregnancy was associated with the greatest reduction in estimated ASD risk (RR, 0.36; 95% CI 0.15-0.84; P = .02).

The researchers say their findings suggest that maternal intake of folic acid during the first month of pregnancy may reduce incidence of ASD recurrence in younger siblings of children with the condition. However, they urge that more studies be done to see if their results can be replicated. Future studies, they said, should focus on the impact of specific nutrients from vitamin supplements and food sources, diet quality, dose thresholds, interactions with genetic variants, and potential mechanisms of action.